Resting-state connectivity studies as a marker of the acute and delayed effects of subanaesthetic ketamine administration in healthy and depressed individuals: A systematic review
Vasileia Kotoula, T. Webster, James Stone, Mitul A. Mehta
Brain and Neuroscience Advances 2021 DOI: 10.1177/23982128211055426 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Esketamine Ketamine |
| Key findings | The authors conclude that depression is associated with altered connectivity in emotion-regulation and reward areas and increased default mode network connectivity relative to healthy controls, though this latter finding is less prominent than the literature often assumes. Acute ketamine increases connectivity in healthy volunteers, while delayed effects vary in direction and appear consistent with normalization of depression-related changes; limited studies and heterogeneous methods prevent firm conclusions. |
Abstract
Acute ketamine administration has been widely used in neuroimaging research to mimic psychosis-like symptoms. Within the last two decades, ketamine has also emerged as a potent, fast-acting antidepressant. The delayed effects of the drug, observed 2–48 h after a single infusion, are associated with marked improvements in depressive symptoms. At the systems’ level, several studies have investigated the acute ketamine effects on brain activity and connectivity; however, several questions remain unanswered around the brain changes that accompany the drug’s antidepressant effects and how these changes relate to the brain areas that appear with altered function and connectivity in depression. This review aims to address some of these questions by focusing on resting-state brain connectivity. We summarise the studies that have examined connectivity changes in treatment-naïve, depressed individuals and those studies that have looked at the acute and delayed effects of ketamine in healthy and depressed volunteers. We conclude that brain areas that are important for emotional regulation and reward processing appear with altered connectivity in depression whereas the default mode network presents with increased connectivity in depressed individuals compared to healthy controls. This finding, however, is not as prominent as the literature often assumes. Acute ketamine administration causes an increase in brain connectivity in healthy volunteers. The delayed effects of ketamine on brain connectivity vary in direction and appear to be consistent with the drug normalising the changes observed in depression. The limited number of studies however, as well as the different approaches for resting-state connectivity analysis make it very difficult to draw firm conclusions and highlight the importance of data sharing and larger future studies.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cited by 14
- Brain-based correlates of antidepressant response to ketamine: a comprehensive systematic review of neuroimaging studies. The Lancet Psychiatry October 1, 2023
- Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review Frontiers in Psychiatry May 26, 2022
- Neuroimaging-Derived Biomarkers of the Antidepressant Effects of Ketamine Biological Psychiatry: Cognitive Neuroscience and Neuroimaging November 25, 2022
- Measuring acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans using TD-fNIRS. Scientific Reports July 19, 2023
- Neurocognitive effects of subanesthetic serial ketamine infusions in treatment resistant depression. Journal of Affective Disorders April 1, 2023
and 9 more in the library
Cites 20
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine Archives of General Psychiatry September 1, 2005
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action PLoS One September 24, 2012
and 15 more in the library